We continue to examine the possible role of genetic susceptibility in the etiology of lung cancer in two distinct studies. The first is a case-control study of African-Americans and Caucasians in Los Angeles County. Subject enrollment (356 cases and 731 control subjects) was completed by S. London while she was a faculty member at University of Southern California. We are currently analyzing data on the combined polymorphisms of GSTT1, GSTM1 and microsomal epoxide hydrolase. We have plans to use these samples to examine other polymorphisms. In the past year, we published the first report of an association between the myeloperoxidase genetic polymorphism and lung cancer risk. This polymorphisms is of interest because it effects both carcinogen metabolism and oxidative stress. Collection of archival tissue samples is nearly complete which will enable us to examine somatic mutations in tumor suppressor genes. We have also published on other putative risk factors in this dataset in the past year including alcohol intake and smoking of menthol cigarettes. We also also participating in an international collaborative project to pool original data from studies of genetic polymorphisms and lung cancer risk. The other study is a cohort study of 18,244 Shanghai men (Ronald Ross, USC, PI). The DNA source is from serum. Laboratory analysis of the GSTT1 and M1 polymorphisms on these samples is complete and analysis of the exon 7 polymorphisms of CYP1A1 is underway. The epidemiologic analysis will begin once these data are available. We are also doing a comparative analysis of the risk of lung cancer in relation to smoking parameters in this cohort compared to a large cohort of US Caucasian men to examine the hypothesis proposed by others that the risk of smoking related lung cancer is lower in Asian populations. Analysis of the potential role of IGF1 is also beginning.